Alcoholism (alcohol abuse and dependence) is a common disorder with a peak age of onset in early adulthood and a complex etiology. Twin studies comprised predominantly of participants of European Caucasian ancestry have shown genetic factors contribute 40-60 percent of the risk for the development of alcohol dependence in both sexes. Yet, very little is currently known about how genetic influences on alcoholism are mediated or moderated (e.g., gene-environment interactions). The aldehyde dehydrogenase ALDH2 gene, to date, has the strongest and most consistent associations with alcohol dependence. The variant ALDH2*2 allele is found in high prevalence, and almost exclusively, in Asian populations. Using a sample of 18-19 year-old Chinese and Korean American college students, the proposed study aims to prospectively test key elements of a mechanistic pathway hypothesized to explain how possession of ALDH2*2 alleles protect individuals against alcohol use disorders (AUDs). It is hypothesized ALDH2*2 will lead to heightened responses to alcohol, reduced positive expectancies about alcohol, and decreased rates of use, heavy use, and adverse drinking consequences. The proposed study also aims to test for potential moderators of the relationships between ALDH2*2 and alcohol involvement variables. It is hypothesized that being female, Korean, highly acculturated, highly religious, highly antisocial, highly behaviorally undercontrolled, with greater negative affect, with a family history of AUDs, with parents who drink more heavily, with siblings who drink more heavily, with peers who drink more heavily, and without ADH1B*2 alleles will decrease the effect sizes of ALDH2*2. An exploratory aim of the proposed study is to examine other ADH and ALDH gene polymorphisms for associations with alcohol involvement variables. Findings from this research will provide important information about the developmental course of alcohol use and alcohol problems in an understudied population, Asian American men and women, during a period of high environmental risk for drinking behavior (college attendance). The identification of gene modifiers using explicitly measured variables will provide a more comprehensive understanding of the complex interplay of factors and processes involved in the etiology of alcohol involvement. PUBLIC HEALTH RELEVANCE: Results from this study will contribute to a more comprehensive understanding of the causal relationship between the ALDH2 gene and the progression of alcohol-related behaviors, as well as the complex interplay of factors and processes involved in the etiology of alcohol involvement. Insofar as much remains to be learned about the etiology of alcoholism in the general population, these findings will contribute to a greater understanding of racial and ethnic disparities in the causes and consequences of alcohol involvement and the generalizability of findings across groups. Through this understanding, findings from the proposed research have the potential to lead to more effective prevention of alcoholism.